Ranitidine is a best-selling drug used to reduce high stomach acid. Through its lowering effect on stomach acid, it is widely used in the treatment of conditions such as gastroesophageal reflux, ulcers in the stomach and bowel, erosive esophagitis, and Zollinger-Ellison syndrome. Read on to learn more about this medication, its health benefits, and main adverse effects.
Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.
What Is Ranitidine (Zantac)?
Ranitidine is a drug that decreases stomach acid production and is therefore employed in the treatment and prevention of disorders related to excessive stomach acid .
Developed in 1977, ranitidine was first introduced into the market in 1981 and quickly became the best-selling drug worldwide .
The main brand names for ranitidine are Zantac® and Taladine®.
Prescription ranitidine comes as tablets (oral and effervescent), capsules, and syrup. This medication is mainly used to treat :
- Ulcers of the stomach and bowel
- Esophagus inflammation
- Gastroesophageal reflux disease (GERD)
- Zollinger-Ellison syndrome
- Acid indigestion
Mechanism of Action
Histamine is a compound that is produced by white blood cells (mast cells and basophils), platelets, immune cells (lymphocytes), brain cells, and secreting cells in stomach glands (enterochromaffin cells) .
In the stomach, histamine is produced by enterochromaffin cells and activates those that produce acid (parietal cells) by binding to the H2-receptors on their surface .
Ranitidine and other H2-receptor blockers were designed by using histamine as a starting point and modifying its chemical structure .
These chemicals compete with histamine for binding to the H2-receptor. The reversible interaction between a blocker and the receptor prevents the binding of histamine, and thus the activation of acid production .
Uses of Ranitidine
Over-the-counter ranitidine is approved to prevent and relieve heartburn associated with acid ingestion and sour stomach. Prescription ranitidine is mainly approved for the treatment and prevention of ulcers of the stomach and intestines and gastroesophageal reflux disease.
Follow your doctor’s instructions carefully. Take ranitidine as recommended and do not change its dose and frequency or stop taking it without your doctor’s approval. Your healthcare provider may recommend you combine ranitidine with other medications (such as antacids and PPIs). Talk to your doctor if your condition doesn’t improve or if it worsens.
1) Gastroesophageal Reflux Disease (GERD)
Gastroesophageal reflux disease (GERD) is the abnormal entry of stomach acid into the esophagus. The main symptoms of this disease, which affects 20% of the US adult population at least once a week, are heartburn and regurgitation .
Low doses of ranitidine decreased stomach acid for 9 hours in a small trial on 24 healthy people .
However, a small trial on 18 people with GERD showed the development of tolerance to the medication after long-term treatment with ranitidine, resulting in a reduced efficiency .
In a small trial on 29 children, low doses of ranitidine reduced stomach acid .
In a small trial on 18 pregnant women, ranitidine twice daily relieved GERD symptoms more efficiently than the same dose once daily .
However, PPIs generally outperform ranitidine in the treatment of this disease.
Both ranitidine and omeprazole were equally efficient in treating GERD symptoms in a clinical trial on 76 children .
Heartburn is a burning and painful sensation in the chest and upper stomach that is normally due to the entry of stomach acid into the esophagus, and is the main symptom of gastroesophageal reflux disease (GERD) .
Heartburn is generally well controlled with antacids. While H2-receptor blockers and PPIs prevent the formation of acid in the stomach, antacids neutralize it after its production .
In a clinical trial on almost 100 people with self-perceived heartburn taking either an antacid (Maalox) or ranitidine, the antacid was faster in relieving heartburn symptoms .
In a small trial on 26 people with frequent meal-induced heartburn, ranitidine was faster at reducing stomach acidity, while the effect of the antacid (calcium carbonate) was faster in the esophagus .
In a longer-term trial on over 150 people suffering from heartburn frequently, ranitidine was more effective than antacid (calcium carbonate) in relieving heartburn, curing erosive esophagitis, reducing pain, and improving life quality .
However, doubling the dose to 300 mg did not improve the recovery rate in the first trial .
3) Erosive Esophagitis
A small proportion of people with gastroesophageal reflux disease (GERD) develop erosive esophagitis, in which the lining of the esophagus is inflamed and worn away .
Those whose esophagus is in contact with stomach acid for extended periods have the highest risk of developing erosive esophagitis .
In a small trial on 7 people with erosive esophagitis, low doses of ranitidine decreased the exposure of the esophagus to acid, but failed to reduce it to normal values .
In a trial on almost 400 people with erosive esophagitis being treated with proton pump inhibitors (PPIs), adding ranitidine improved heartburn symptoms in the short term, but patients eventually developed tolerance .
4) Zollinger-Ellison Syndrome
Zollinger-Ellison syndrome is the presence of a tumor, normally in the pancreas, bowel, or nodes on the stomach, which produces a hormone (gastrin) that stimulates the increased release of stomach acids .
The symptoms are caused by the excess of acid and include :
- Ulcers in the bowel
- Gastroesophageal reflux
- Loss of appetite
Excessive acid production can be treated with H2-receptor blockers. Due to its low side effects and limited interactions with other drugs, ranitidine is often the treatment of choice .
Ranitidine has also been effectively used in managing Zollinger-Ellison syndrome in pregnant women .
5) NSAID-Induced Complications
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to treat inflammatory conditions and reduce pain. Their long-term use is associated with increased risk of developing ulcers in the stomach and bowel [63, 64].
Given their stronger action, PPIs have been included in trials comparing their efficiency to that of ranitidine against NSAID-induced ulcers.
In a clinical trial of over 500 people on NSAID with ulcers in the stomach or bowel, omeprazole was more effective than ranitidine in healing and preventing ulcers .
The efficiency of esomeprazole in healing NSAID-induced stomach ulcers was higher in people taking esomeprazole than in those taking ranitidine in one trial on over 400 people, but comparable in a similar one [75, 76].
Critically ill patients, such as those in intensive care units, are more prone to stomach ulcers .
Because stress-induced ulcers are uncommon at low acid levels in the stomach, H2-receptor inhibitors are very popular for prevention of ulcers .
In a small trial on 37 people in intensive care units, ranitidine efficiently reduced stomach acidity, thus preventing the appearance of stress-induced ulcers .
In another trial on 48 newborn babies in the neonatal intensive care unit, short-term treatment with ranitidine prevented the appearance of stomach ulcers .
However, in a trial on almost 100 people in intensive care units with normal liver and kidney function subjected to long-term mechanical ventilation, ranitidine did not decrease the incidence rate of stress-induced ulcers .
In a meta-analysis of 3 studies, omeprazole was as effective as ranitidine in the prevention of stress-induced ulcers .
In contrast, sucralfate (a drug that binds to ulcers and creates a protective barrier against stomach acids) was at least as effective as ranitidine in preventing the appearance of stress-induced ulcers and reduced the risk of pneumonia in 2 trials [84, 85].
Stomach and Intestinal Ulcers
Ulcers are breaks in the lining of the stomach or first part of the small intestine.
The main symptoms are :
- Stomach pain
- Loss of appetite
- Vomiting of blood
- Weight loss
Helicobacter Pylori-Induced Ulcers and Complications
Helicobacter pylori is a bacteria that infects the digestive system. Although most infected individuals do not show symptoms of disease, infection with this bacteria is responsible for most ulcer cases diagnosed .
Ranitidine bismuth citrate, previously sold under the brand name Titrec® and now available as a generic drug, is an effective treatment against H. pylori-induced ulcers. This drug combines the acid-decreasing action of ranitidine and the antimicrobial and mucosal-protective roles of bismuth .
The combination of ranitidine bismuth citrate with the antibiotic clarithromycin was more effective in healing ulcers and eradicating H. pylori than ranitidine bismuth citrate alone in several studies [104, 105, 106, 107].
A clinical trial on over 200 people showed that amoxicillin could be used as an alternative to clarithromycin in those intolerant or resistant to this antibiotic .
In a trial on over 500 people with duodenal ulcer and H. pylori infection, a dual therapy with clarithromycin and omeprazole was as effective as one with this antibiotic and ranitidine bismuth citrate .
However, ranitidine bismuth citrate in triple therapy with amoxicillin and clarithromycin eradicated H. pylori more efficiently than all PPIs except rabeprazole in a trial on almost 400 people .
7) Prevention of Acid Aspiration During Surgery
Acid aspiration is the inhalation of regurgitated stomach acids into the lungs. This complication may occur during surgical procedures .
Acid aspiration is particularly harmful to patients when the stomach is full and the acid level is high .
In a trial on almost 300 people about to undergo surgery, ranitidine twice per day reduced both stomach content volume and acid levels .
In another trial on 75 children, intake of water plus ranitidine prior to surgery reduced their risk of acid aspiration and improved their behavior .
The combination of ranitidine with pirenzepine reduced both stomach content volume and acidity in a clinical trial on over 100 children .
8) Inhibition of Allergic Response
Because they prevent histamine activity, H2-receptor blockers like ranitidine may reduce the allergic response to some agents .
Henoch-Schönlein vasculitis is the inflammation of blood vessels caused by the allergic reaction to infections or drugs.
Its main symptoms include :
- Red- or purple-colored spots on the skin
- Stomach pain
- Stomach and bowel bleeding
- Blood in the urine
In a small trial on 12 people with Henoch-Schönlein vasculitis, treatment with ranitidine reduced the duration and severity of stomach pain and bleeding .
9) Gut Bleeding
Gut bleeding is a condition in which blood vessels of the stomach, esophagus, or bowel are broken. It can be life-threatening if it affects large vessels .
Its most common causes are:
- Ulcers in the stomach and bowel 
- Mallory-Weiss tear 
- Stress-induced stomach inflammation 
- Dieulafoy lesions 
- Dilated veins in the stomach 
However, omeprazole was more effective than ranitidine in treating upper gut bleeding in a trial on almost 100 people .
In a multi-center trial on 1200 people requiring mechanical ventilation, ranitidine reduced gut bleeding more efficiently than sucralfate .
Insufficient Evidence for:
Colorectal Cancer Therapy
H2-receptor blockers may prevent 3 cancer-promoting effects of histamine:
- Increased activity of immune-suppressing cells 
- Prevention of tumor recognition by immune cells 
- Promotion of cancer cell growth 
In a trial on over 500 people with cancer in the large bowel who underwent tumor removal, treatment with ranitidine for 5 years improved survival in those who did not receive blood transfusions during the surgical procedure .
In cell trials, ranitidine reduced the growth and increased the death of colorectal cancer cells .
However, the research is still preliminary and further studies should determine if ranitidine is a helpful aid in colorectal cancer prevention.
The two main types of IBD are :
The main symptoms common to both types of IBD are:
By preventing the action of histamine, H2-receptor blocking like ranitidine may improve the symptoms of bowel inflammation. However, this potential benefit is only a speculation based on ranitidine’s mechanism. Clinical trials on people with IBD should confirm it.
Ranitidine is frequently used worldwide and generally well tolerated.
A review of 21 trials concluded that ranitidine doses of 150 to 600 mg/day are equally safe in elderly and non-elderly patients .
Frequency of the main adverse effects of ranitidine in elderly and non-elderly patients .
Adverse effects can, however, occur in up to 5% of patients. Those most frequently reported are :
1) Stomach and Bowel
The most frequent events in this system are :
- Nausea and/or vomiting (2.6-6.8%)
- Diarrhea (1.4-4.1%)
- Stomach pain (1.3-1.8%)
These effects tend to improve with continuous treatment. Other, less frequent (up to 2%) side effects include:
- Dry mouth
- Pancreas inflammation
Stomach and bowel cancer occurred at a rate of 0.2 per million patients treated, but cannot be associated with ranitidine intake .
The most common effects of ranitidine on the brain are :
- Confusion (2.1 events per million)
- Headache (2.1 events per million)
- Dizziness (1.7 events per million)
The proportion increases with age and among hospitalized patients, as well as in those with liver or kidney failure. The symptoms are quickly reversed by stopping the treatment .
Less frequently reported reactions include:
Skin reactions associated with ranitidine intake include :
- Rash (2.9 events per million)
- Itching (1.9 events per million)
- Hives (1.7 events per million)
- Baldness (1.3 events per million)
The following reactions have been observed less frequently:
- Toxic skin necrolysis (0.08 events per million) 
- Stevens-Johnson syndrome (0.07 events per million) 
Liver injuries caused by the use of ranitidine are rare .
The most common liver abnormalities associated with ranitidine are :
- Increased levels of liver enzymes (5.9 events per million)
- Hepatitis (1.1 events per million)
5) Hormone Production
Breast growth has been reported in 0.2 to 1.3 male patients per million .
The most common effects (0.2 to 0.3 events per million) on the heart include :
However, no differences were found between the ranitidine and placebo treatment groups .
7) Blood Composition
In very rare cases, patients taking ranitidine had lower counts of white blood cells and platelets. However, the incidence was lower than that found in the general population .
Although ranitidine is mostly eliminated through the urine, no evidence of kidney damage associated with this drug has been found. Dose reduction is only recommended in patients with strong kidney failure .
On very rare occasions, patients taking ranitidine have developed a gout-like joint inflammation .
One patient suffered from airway narrowing, breath shortness, and cough after taking ranitidine .
One case of a male patient suffering from impotence during treatment with ranitidine was reported .
To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. Talk to your healthcare provider to find out how ranitidine might interact with something else you are taking.
Due to its acid-blocking activity, ranitidine reduces the absorption of drugs requiring acid in the stomach, such as:
- HIV medication (Atazanavir, Delavirdine, and Fosamprenavir) [185, 186, 187]
- Antifungal drugs (Itraconazole and Ketoconazole) [188, 189]
- Cancer medication (Gefitinib, Dasatinib, and Erlotinib ) [190, 191, 192]
- Antibiotics (Enoxacin, Cefpodoxime, Bacampicillin, and Cefuroxime) [193, 194, 195, 195]
Conversely, it increases the absorption of drugs requiring low acid, such as the sedatives:
In a small trial on 12 healthy volunteers, ranitidine increased absorption of the HIV medication saquinavir. However, the effect was independent of ranitidine’s activity against acid production .
Absorption of ranitidine and other H2-receptor blockers is reduced by:
- Antacids 
- Cisapride (enhancer of stomach and bowel movements) 
- Sucralfate (ulcer medication) 
- Procainamide (treatment of irregular heart rates) 
- Triamterene (treatment of hypertension and fluid retention) 
- Midazolam (sedative) 
It is thus important to adjust the doses of these medications when used in combination with ranitidine.
The safety and efficiency of this drug have not been sufficiently described in patients younger than 1 month .
In a small trial on 29 children aged 4 to 11 years old with stomach acidity, 75 mg/day ranitidine was both effective and safe .
The incidence of the most common side effects on the nervous system (confusion, headaches, and dizziness) increased in elderly and chronically ill patients, as well as in those with kidney failure [212, 165].
In critically ill patients, ranitidine may increase the risk of developing pneumonia .
In rare occasions, ranitidine has been reported to cause:
Therefore, it should be avoided in people already suffering from these conditions.
Because ranitidine is mostly eliminated through urine and partly broken down in the liver, patients with severe kidney and liver diseases should avoid or moderate its intake .
Ranitidine is significantly removed by hemodialysis and therefore should be taken after this procedure .
Finally, ranitidine must be avoided by patients with an allergy to H2-receptor blockers .
Use During Pregnancy and Breastfeeding
A study of pregnancy databases including over 1000 women exposed to H2-receptor blockers concluded that these drugs are safe, given their lack of association with :
- Infant risk of dying
- Premature delivery
- Low birth weight
- Poor infant wellness (low APGAR scores)
Ranitidine is transported into breast milk. Because the peak concentration occurs 12 hours after intake, breastfeeding is recommended 1 to 2 hours after drug use to reduce exposure to the baby .
Forms and Dosage
- Tablets: 75, 150, and 300 mg
- Capsules: 150 and 300 mg
- Syrup: 75 mg/5 ml
The most common over-the-counter doses to treat and prevent heartburn and acid indigestion are 75 and 150 mg per use per day .
Doubling the standard dose to 300 mg of ranitidine twice per day does not improve its efficiency in treating gastroesophageal reflux symptoms .
In people suffering from stomach and bowel ulcers, one single dose of 300 mg ranitidine daily is as effective as two doses of 150 mg per day .
In the treatment of erosive esophagitis, the recommended doses are ranitidine 300 mg twice daily or 150 mg per day 4 times daily .
Zollinger-Ellison syndrome can be treated with very high doses (up to 2.1 g ranitidine per day) .
Ranitidine is very safe and doses up to 6 g per day are generally well tolerated .
Limitations and Caveats
The evidence for the effects of ranitidine on skin allergic reactions is based on a few studies of a relatively small size with a certain risk of bias .
More evidence is needed to evaluate the efficiency of ranitidine in colorectal cancer therapy .
PPIs Versus H2-Receptor Blockers
Stomach acid is produced by the presence of protons (H+).
This enzyme is found inside parietal cells in the inner lining of the stomach. Upon binding of histamine to the H2-receptors on these cells, the H+/K+ ATPase moves to the cell surface and turns into its activated shape .
Because they target the last step of acid production and block the enzyme, the effect of PPIs is stronger and lasts longer than that of H2-receptor blockers .
PPIs are sold as inactive, neutrally charged drugs that cross membranes and accumulate in parietal cells. The high acidity in these cells then transforms PPIs into their active form, which binds to the H+/K+ ATPase and blocks it .
The main commercial drugs belonging to this category are :
- Omeprazole (Losec®)
- Lansoprazole (Prevacid®)
- Pantoprazole (Protonix®)
- Rabeprazole (Aciphex®)
- Esomeprazole (Nexium®)
- Dexlansoprazole (Dexilant®)
H2-receptor blockers are thus preferred to treat mild, occasional symptoms (episodic heartburn and acid indigestion, or acid aspiration during surgery), while PPIs are used with stronger, chronic disorders (chronic gastroesophageal reflux disease, erosive esophagitis, and ulcers) [238, 239, 240].
Because of their stronger action, PPIs showed increased efficiency over H2-receptor blockers in clinical trials on people with:
- Gastroesophageal reflux disease 
- Acid indigestion 
- Erosive esophagitis 
- Stress-induced ulcer 
Although both H2-receptor blockers and PPIs are usually well tolerated, it is important to take their differential adverse effects into consideration. Some risks associated with long-term treatment with PPIs include:
- Magnesium deficiency 
- Increased risk of hip fracture 
- Bacterial infections in the digestive system [246, 247, 248]
- Pneumonia 
- Chronic kidney disease 
- Dementia 
Ranitidine vs. Other H2-Receptor Blockers
Besides ranitidine, the commercial H2-receptor blockers most widely employed are :
- Cimetidine (Tagamet®)
- Famotidine (Pepcid®)
- Nizatidine (Axid®)
Ranitidine vs. Cimetidine
Cimetidine is available in 200, 300, 400, and 800 mg tablets, as a syrup (200 mg/5 ml), as a 100 or 200 mg/5 ml suspension, as intravenous injection (100 mg/ml), and as intravenous infusion (4 mg/ml). Cimetidine is 4 to 5 times less powerful than ranitidine .
In a trial on over 1000 people with gastroesophageal reflux, a 200-mg dose of cimetidine was as efficient as 75 mg of ranitidine in reducing heartburn symptoms .
In another trial on almost 200 children with acid indigestion, treatments with ranitidine (1 to 2 mg/kg per dose) and cimetidine (10 mg/kg per dose) were equally effective in relieving the symptoms .
Additionally, 7.8 g cimetidine/day reduced the symptoms as efficiently as 2.1 g ranitidine/day in a small trial on 9 people with Zollinger-Ellison syndrome .
Cimetidine (200 mg 3 times per day) was as effective as ranitidine (150 mg twice per day) in healing stomach ulcers in one trial on 260 people .
Ranitidine vs. Famotidine
In a small trial on 9 people with Zollinger-Ellison syndrome, 0.24 g famotidine/day was as efficient at reducing the symptoms as 2.1 g ranitidine/day, and its effects lasted 30% longer .
However, famotidine (40 mg/day) was less effective in treating stomach ulcers than ranitidine (150 mg twice per day) in one trial on 69 people .
Both ranitidine and famotidine showed similar effectiveness against acid aspiration in a trial on 50 people undergoing surgery .
Ranitidine vs. Nizatidine
Nizatidine is as potent as ranitidine and is available as 150- and 300-mg capsules .
In a small trial on 10 elderly people, repeated intake of nizatidine caused lower accumulation of the drug in blood than the same treatment with ranitidine. Nizatidine was thus concluded to be safer for the repeated treatment of elderly patients .
In 2 trials on over 400 people with gastroesophageal reflux, ranitidine 150 mg was as effective as nizatidine 150 mg at relieving the heartburn and acid regurgitation symptoms .
Genetics Related to Ranitidine
OCT1 is responsible for transporting ranitidine into the liver for its subsequent degradation. Alleles with poor or absent ranitidine uptake capacity may reduce the breakdown of this drug .
SNPs associated with lower abundance of FMO3 (rs2064074, rs28363536, rs2266782, rs909530, rs2266780, and rs909531) may reduce ranitidine breakdown .
CYP1A2 alleles may be less efficient at breaking down ranitidine based on their reduced activity on other drugs. In turn, the CYP1A2*1F variant caused increased activity of this enzyme [268, 269, 270, 271].
If You Have Food Sensitivities
I recommend following my lectin avoidance diet, named as such because I think that lectins are the single major trigger of autoimmune disease. However, they are not the only trigger. And this diet is not a one-size-fits-all regimen. It may not suit EVERYONE’s needs, but it’s a good template from which to build a personalized diet.
If you suffer from food sensitivities, the Lectin Avoidance Diet helps you figure out which foods are inflammatory, and which are less inflammatory for you.